Treatment seeking for marijuana dependence has dramatically increased. The majority of marijuana dependent outpatients do not achieve abstinence, and many attribute this to withdrawal symptoms. Despite this, many continue to believe marijuana has little dependence potential. Our and others research has validated a marijuana withdrawal syndrome. What remains unclear and is the overarching aim of this competing continuation is the clinical importance of the marijuana withdrawal syndrome. We propose to extend our programmatic research by conducting four outpatient studies. Studies 1A and 1B will directly compare marijuana withdrawal to a recognized clinically important withdrawal syndrome, i.e., tobacco withdrawal. Study 1A will maximize internal validity by using a within-subjects design to compare these two syndromes in those who use both substances daily. This experiment also will examine withdrawal that occurs when participants stop using both marijuana and tobacco simultaneously. Study 1B will maximize external validity in a between-groups study comparing withdrawal in those who smoke only marijuana or only tobacco. Study 2 will be the first prospective, systematic study of marijuana withdrawal in a clinical sample, adults seeking treatment for marijuana-dependence. Withdrawal will be assessed for 21 days postcessation, and effects compared to that observed with non-treatment seekers. Study 3 will be the first to systematically assess and characterize marijuana withdrawal among adolescents seeking treatment for marijuana dependence, a clinical population that comprises almost half the treatment cases for marijuana dependence. Again symptoms of withdrawal will be assessed for 21days post-cessation. These clinical studies will also initially explore whether greater withdrawal severity or duration predicts relapse. In summary, the proposed research will use methods developed in our original funding period to determine the clinical significance of marijuana withdrawal in both adults and adolescents. Such information will be vital to determining whether marijuana withdrawal should be included in the DSM and to determining the dependence potential of marijuana. This information will also help decide whether pharmacological treatments for marijuana dependence focused on relieving withdrawal should be pursued.